A systematic review and meta-analysis of the efficacy of vonoprazan for proton pump inhibitor-resistant gastroesophageal reflux disease.

BACKGROUND AND AIM: Up to 40% of gastroesophageal reflux disease (GERD) patients experience inadequate symptom relief with a proton pump inhibitor (PPI), termed PPI-resistant or refractory GERD. Vonoprazan, a potassium-competitive acid blocker, has better efficacy than PPI in suppressing gastric acid secretion. This meta-analysis summarizes the efficacy and safety of vonoprazan for treating PPI-resistant GERD (both erosive esophagitis [EE] and non-erosive reflux disease [NERD]). METHODS: Four electronic databases (Medline, Embase, SCOPUS, and CENTRAL) were searched for studies indexed until August 1, 2023. Both observational studies and clinical trials assessing the efficacy and safety of vonoprazan in PPI-resistant GERD were included. Efficacy outcomes included healing and maintenance rates of EE and improvement of the Frequency Scale for Symptoms of GERD (FSSG) scores. Serious adverse events (SAEs) were considered a safety outcome. The modified Newcastle-Ottawa Scale (NOS) was used to assess study quality. RESULTS: Twelve studies were included in this meta-analysis. Healing rates of PPI-resistant EE with vonoprazan 20 mg were 91.7% (95% CI 86.8-94.8%) and 88.5% (95% CI 69.7-96.2%) at weeks 4 and 8, respectively. For healed PPI-resistant EE, the overall maintenance rates with vonoprazan 10 mg were 82.6% (95% 61.2-95.0%) at week 8, 86.0% (95% CI 72.1-94.7%) at week 24, and 93.8% (95% CI 69.8-99.8%) at week 48. FSSG scores were improved in 74.6% (95% CI 65.8-81.7%) and 51.9% (95% CI 37.8-65.7%) of patients at weeks 4 and 8. Overall, no SAE was reported. CONCLUSION: Vonoprazan demonstrated high efficacy in the healing and maintenance of PPI-resistant EE and moderate efficacy for the improvement of FSSG score. Vonoprazan was well tolerated in PPI-resistant GERD patients.

The role of magnetic sphincter augmentation in the gastroesophageal reflux disease treatment pathway: the gastroenterology perspective.

Magnetic sphincter augmentation (MSA) is a surgical intervention for well-characterized gastroesophageal reflux disease (GERD), where the esophagogastric junction barrier is augmented using a bracelet of magnetized titanium beads. MSA could be an attractive option for patients with documented GERD who wish to avoid long-term pharmacologic therapy or whose symptoms are not adequately managed with lifestyle modifications and pharmacologic therapy. The 'ideal' MSA patient is one with prominent regurgitation, without dysphagia or esophageal motor dysfunction, with objective evidence of GERD on upper endoscopy and/or ambulatory reflux monitoring. Appropriate candidates with significant hiatus hernia may pursue MSA with concomitant hiatus hernia repair. The increasing adoption of MSA in the GERD treatment pathway reflects research that shows benefits in long-term outcomes and healthcare costs compared with other established therapies in appropriate clinical settings.

Endoscopic management of gastroesophageal reflux disease: Panacea for proton pump inhibitors dependent/refractory patients.

Endoscopic therapies in proton pump inhibitors (PPI) dependent/refractory gastroesophageal reflux disease (GERD) are increasingly indicated in patients who are not suitable or willing for chronic medical therapy and surgical fundoplication. Currently available endoluminal anti-reflux procedures include radiofrequency therapy (Stretta), suturing/plication and mucosal ablation/resection techniques at the gastroesophageal junction. Meticulous work up and patient selection results in a favorable outcome with these endoscopic therapies, especially the quality of life and partially the PPI independence. Stretta can be considered in patients with PPI refractory GERD and might have a role in patients with reflux hypersensitivity and functional heartburn. Endoscopic fundoplication using the Esophyx device and the GERD-X device have strong evidence (multiple randomized controlled trials) in patients with small hiatus hernia and high volume reflux episodes. Mucosal resection/ablation techniques like anti-reflux mucosectomy and anti-reflux mucosal ablation have shown promising results but need long term follow-up studies to prove their efficacy. The subset of PPI dependent GERD population will benefit from endoscopic therapies and the future of endoscopic management of GERD looks promising.

Clinical utility of salivary pepsin measurement in patients with proton pump inhibitor-refractory gastroesophageal reflux disease symptoms: a prospective comparative study.

BACKGROUND: Salivary pepsin measurement has been reported to be useful for diagnosing gastroesophageal reflux disease (GERD). This study aimed to clarify the usefulness of salivary pepsin measurement in patients with proton pump inhibitor (PPI)-refractory GERD symptoms without erosive esophagitis. METHODS: One hundred and two patients were included. Over seven days after terminating PPI treatment, all patients underwent a 24-h pH-impedance test and salivary pepsin measurement. In patients whose main symptoms included laryngopharyngeal symptoms, a hypopharyngeal multichannel intraluminal impedance (HMII) test was performed, whereas in other patients, a conventional combined multichannel intraluminal impedance-pH (MII-pH) test was performed. In the HMII tests, patients were divided into abnormal proximal exposure (APE) and non-APE groups. Salivary pepsin concentrations were compared according to acid exposure time (AET) values and were also compared between the APE and non-APE groups. RESULTS: The median salivary pepsin concentration in patients with AET > 6% was significantly higher than that in patients with AET ≤ 6% (345.0 [170.0-469.3] ng/mL vs. 120.0 [97.0-290.1] ng/mL, p < 0.01). The sensitivity, specificity, positive predictive value, and negative predictive value of a positive test (> 109 ng/mL) to diagnose patients with AET > 6% were 75.0%, 51.3%, 32.1%, and 86.9%, respectively. There was no significant difference between concentrations in the APE group and concentrations in the non-APE group. CONCLUSIONS: In patients with PPI-refractory nonerosive reflux disease, salivary pepsin measurement may help diagnose patients who have conclusive evidence of reflux, whereas it is not adequate for identifying patients with APE.

Refractory Heartburn: A Challenging Problem in Clinical Practice.

Gastroesophageal reflux disease (GERD) is a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications. Heartburn and regurgitation are the typical symptoms of GERD. The treatment of GERD encompasses lifestyle modifications, pharmacological, endoscopic, and surgical therapy. The majority of the patients respond to 4-8 weeks of proton-pump inhibitors therapy, but 20-42% will demonstrate partial or complete lack of response to treatment. While these patients have been considered as having refractory heartburn, a subset of them does not have GERD or have not been adequately treated. The main causes of refractory heartburn include: poor compliance; inadequate proton-pump inhibitors dosage; incorrect diagnosis; comorbidities; genotypic differences; residual gastroesophageal reflux; eosinophilic esophagitis and others. Treatment is commonly directed toward the underlying cause of patients' refractory heartburn.

Association between CYP2C19 extensive metabolizer phenotype and childhood anti-reflux surgery following failed proton pump inhibitor medication treatment.

When pediatric gastroesophageal reflux disease (GERD) that is refractory to proton pump inhibitor (PPI) medication treatment is identified in clinical practice and anti-reflux surgery (ARS) is being considered, genetic factors related to PPI metabolism by the CYP2C19 enzyme are currently not part of the clinical decision-making process. Our objective was to test the hypothesis that the distribution of the extensive metabolizer (EM) phenotypes among children undergoing ARS after failing PPI therapy would differ compared to controls (children with no history of ARS). We conducted a case-control study between children across the Nemours Health System from 2000 to 2014 who received ARS after failing PPI therapy and a control group comprised of healthy children. Our results demonstrated 2.9% of ARSs vs 20.8% of controls were poor metabolizers (PMs), 55.9% of ARSs vs 49.0% of controls were normal metabolizers (NMs), and 41.2% of ARSs vs 30.2% of controls were EMs; p = 0.035. Next, we performed a multiple-regression model to account for race as a potential confounding variable and the EM group was significantly associated with ARS compared to controls (OR 9.78, CI 1.25-76.55, p < 0.03). CONCLUSION: Among children with medically refractory GERD despite PPI therapy, carriage of CYP2C19*17 allele corresponding to the EM phenotype was associated with ARS. Prospective comparative personalized medicine effectiveness studies are needed to determine if CYP2C19 genotype-guided dosing improves response to PPI therapy without a corresponding increase in adverse effects in children. What is known: • Anti-reflux surgery (ARS) is one of the most common surgical procedures performed in children for the indication of refractory gastroesophageal reflux disease (GERD). What is new: • Individualizing PPI medication dosing based on CYP2C19 diplotype may avoid GERD treatment failures and reduce the need for anti-reflux surgery (ARS).

A scientometrics analysis and visualization of refractory gastroesophageal reflux disease.

Background: Refractory gastroesophageal reflux disease (refractory GERD) is a heterogeneous disease characterized by unresponsiveness or poor efficacy to proton-pump inhibitors (PPIs). This chronic disorder substantially weakens patients' mental wellbeing and quality of life, increasing the financial burden on society. Multiple articles have been reported in this area. However, literature involving scientometric analysis of refractory GERD is absent. Therefore, it is necessary to understand the evolution of research themes and the main hotspots of refractory GERD through bibliometric methods. Methods: All documents related to refractory GERD based on the WOS Core Collection from January 2000 to November 2023 were selected for analysis. Citespace V 6.1 R6, VOSviewer V 1.6.20, and Scimago Graphica V 1.0.38 were used to perform bibliometric analysis. Results: We collected a total of 241 research articles from 36 countries and 322 institutions, contributed by over 1,000 authors. Over the last 20 years, the number of articles in this field has increased year by year, and since 2011, the number of publications has increased dramatically, with 85.89% of the papers. These countries are led by the United States and Japan. GUT had the highest number of citations and DIGESTION had the highest number of publications. Research on standardized diagnosis and management, mechanisms, novel monitoring methods, and innovative drugs and procedures for refractory GERD are the main topics and hotspots in this field. This study also found that neuroimmune interaction is closely related to refractory GERD, which may be a new direction for future mechanism research. Conclusion: Our study is the first bibliometric analysis of the global literature on refractory GERD. This research provides valuable insights for researchers, enabling them to quickly understand the research frontier and hot topics of this field.

Refractory Gastroesophageal Reflux Disease: Diagnosis and Management.

Gastroesophageal reflux disease (GERD) is common, with increasing worldwide disease prevalence and high economic burden. A significant number of patients will remain symptomatic following an empiric proton pump inhibitor (PPI) trial. Persistent symptoms despite PPI therapy are often mislabeled as refractory GERD. For patients with no prior GERD evidence (unproven GERD), testing is performed off antisecretory therapy to identify objective evidence of pathologic reflux using criteria outlined by the Lyon consensus. In proven GERD, differentiation between refractory symptoms (persisting symptoms despite optimized antisecretory therapy) and refractory GERD (abnormal reflux metrics on ambulatory pH impedance monitoring and/or persistent erosive esophagitis on endoscopy while on optimized PPI therapy) can direct subsequent management. While refractory symptoms may arise from esophageal hypersensitivity or functional heartburn, proven refractory GERD requires personalization of the management approach, tapping from an array of non-pharmacologic, pharmacologic, endoscopic, and surgical interventions. Proper diagnosis and management of refractory GERD is critical to mitigate undesirable long-term complications such as strictures, Barrett's esophagus, and esophageal adenocarcinoma. This review outlines the diagnostic workup of patients presenting with refractory GERD symptoms, describes the distinction between unproven and proven GERD, and provides a comprehensive review of the current treatment strategies available for the management of refractory GERD.

Endoscopic anti-reflux mucosectomy (ARMS) and endoscopic anti-reflux ablation (ARMA) as a potential treatment for gastroesophageal reflux - preliminary report.

<b><br>Introduction:</b> Gastroesophageal reflux (GERD) is one of the most common disorders of the alimentary tract. Apart from troublesome symptoms, untreated GERD can lead to Barrett's esophagus and, as a consequence, esophageal adenocarcinoma. As for now, the most common treatment of GERD is PPI pharmacotherapy. However, in a number of cases, this treatment is not sufficient or the patient does not tolerate PPI-group drugs. In such cases, interventional therapy is recommended. So far, laparoscopic fundoplication has been the only suggested option. Other, minimally invasive procedures such as Stretta, MUSE, TIFF, or EsophyX were not recommended due to the lack of clinical data. In 2014, Professor H.Inoue from the Digestive Diseases Center, Showa University in Japan reported on the first series of novel, endoscopic, anti-reflux procedures: anti-reflux mucosectomy (ARMS) and anti-reflux mucosal ablation (ARMA).</br> <b><br>Methods:</b> We conducted our prospective, single-center study in 30 patients (14 female, 16 male) with PPI-refractory GERD. All patients underwent FSSG and GERD-HRQL evaluation and GE junction pressure study prior, 6 weeks and 6 months after the procedures. After the procedure, all patients received PPI treatment for 4 weeks.</br> <b><br>Results:</b> We successfully completed the procedures in all 30 patients. The mean procedure time was 42 minutes. No complications occurred. In 86.67% (26) of our patients, we achieved total remission of GERD symptoms, FSSG scores < 6 and GERD-HRQL scores < 8.</br> <b><br>Conclusions:</b> The results of our study show that ARMS and ARMA are simple, safe, improve GERD-related symptoms, and restore the GE junction's anti-reflux capacity.</br>.

On-therapy impedance-pH monitoring can efficiently characterize PPI-refractory GERD and support treatment escalation.

BACKGROUND: On-therapy impedance-pH monitoring is recommended in patients with documented GERD and PPI-refractory heartburn in order to establish whether the unremitting symptom is reflux-related or not. AIMS: To define on-PPI cut-offs of impedance-pH metrics allowing proper interpretation of on-therapy impedance-pH monitoring. METHODS: Blinded expert review of impedance-pH tracings performed during double-dosage PPI, prospectively collected from 150 GERD patients with PPI-refractory heartburn and 45 GERD patients with PPI-responsive heartburn but persisting extra-esophageal symptoms. Acid exposure time (AET), number of total refluxes (TRs), post-reflux swallow-induced peristaltic wave (PSPW) index, and mean nocturnal baseline impedance (MNBI) were assessed. On-PPI cut-offs were defined and evaluated with ROC analysis and the area under curve (AUC). RESULTS: All the four impedance-pH metrics significantly differed between PPI-refractory and PPI-responsive heartburn cases. At ROC analysis, AUC was 0.73 for AET, 0.75 for TRs, 0.81 for PSPW index, and 0.71 for MNBI; best cut-offs were ≥1.7% for AET, ≥45 for TRs, ≤36% for PSPW index, and ≤ 1847 Ω for MNBI; AUC of such cut-offs was 0.66, 0.71, 0.73, and 0.68, respectively. Analysis of PSPW index and MNBI added to assessment of AET and TRs significantly increased the yield of on-therapy impedance-pH monitoring in the PPI-refractory cohort (97% vs. 83%, p < 0.0001). Notably, suboptimal acid suppression as shown by AET ≥1.7% was detected in 43% of 150 PPI-refractory cases. CONCLUSIONS: We have defined on-PPI cut-offs of impedance-pH metrics by which comprehensive assessment of impedance-pH tracings, including analysis of PSPW index and MNBI can efficiently characterize PPI-refractory GERD and support treatment escalation.

Correlation between Psychosomatic Assessment, Heart Rate Variability, and Refractory GERD: A Prospective Study in Patients with Acid Reflux Esophagitis.

BACKGROUND: Gastroesophageal reflux disease (GERD) affects a significant proportion of individuals, with life stress being a contributing factor. This study aimed to investigate the correlation between psychosomatic evaluations, heart rate variability (HRV), and GERD in a cohort of individuals. Additionally, the study aimed to analyze the sequencing changes following proton pump inhibitor (PPI) treatment and identify predictive factors associated with refractory GERD. METHODS: A prospective cohort of 105 individuals with reflux esophagitis and a control group of 50 participants without acid reflux symptoms were enrolled. Psychosomatic evaluations, including GERDQ, GERDQLQ, RSI, BAI, BDI, and SSS-8, were assessed at baseline and during treatment. HRV parameters were also evaluated. Multivariate analysis was used to identify predictive factors for refractory GERD. PPIs were administered regularly for the initial 2 months and then used on-demand. Refractory GERD was defined as less than 50% improvement in symptom relief or GERDQLQ score ≥ 20 after 8 weeks of PPI treatment. RESULTS: The GERD group had higher scores in all psychosomatic evaluations compared to the control group (all p-values < 0.001). There were no significant changes in any parameters of HRV before and after treatment in the GERD group. Strong and consistent correlations were observed between GERD symptoms and psychological scores (BAI, BDI, and SSS-8) across all time points (W0, W4, and W8). Sequential reductions in GERD symptom scores and psychosomatic evaluations were observed during the initial eight weeks of treatment. Higher GERDQ (≥10) and SSS-8 (≥12) scores were predictive of refractory GERD (p = 0.004 and p = 0.009, respectively). CONCLUSIONS: This study emphasizes the importance of considering physiological and psychological factors in the management of GERD. Psychosomatic evaluations provide valuable insights for assessing and treating GERD patients. Integrating stress management and comprehensive assessments into personalized treatment strategies is crucial.

Clinical profile and characteristics of eosinophilic esophagitis patients presenting with refractory gastroesophageal reflux disease in Makassar, Indonesia.

Refractory Gastroesophageal Reflux Disease (GERD) is a typical GERD that does not respond to Proton Pump Inhibitor (PPI) treatment for 8-12 weeks. One of the differential diagnoses for refractory GERD is eosinophilic esophagitis which is characterized by eosinophilic infiltration into the esophagus endothelium. However, to date, eosinophilic esophagitis is still poorly understood and data is still limited. The aim was to describe the profile and characteristics of patients with eosinophilic esophagitis presenting with refractory GERD in Makassar, Indonesia. This descriptive study involved patients with refractory GERD from two hospitals. In addition to basic demographic data, history, and body mass index, all subjects underwent peripheral blood tests to measure eosinophil level and flexible esophagoscopy, from which esophageal biopsy was done to assess the tissue eosinophil level. Eosinophilic esophagitis was established based on the examination of >15 eosinophils/high power field. Out of 32 subjects, two subjects were diagnosed with eosinophilic esophagitis (6.3%). Both subjects were male with normal BMI in the age range of 36-55 years and none had peripheral blood eosinophilia. Symptoms of eosinophilic esophagitis were similar to refractory GERD. Peripheral blood eosinophilia was not associated with incidence of eosinophilic esophagitis.

Role of Neuromodulators for the Management of Post-Gastric-Fundoplication Dyspepsia: A Retrospective Series.

Post-fundoplication dyspepsia is a common complication of gastric fundoplication surgeries. This can be attributable to the loss of fundal relaxation, decreased gastric accommodation, and/or alterations in gastric motility and sensitivity following fundoplication. The role of neuromodulators in the management of such symptoms is unknown. We retrospectively assessed the efficacy of neuromodulators such as tricyclic antidepressants, buspirone, and mirtazapine for the management of post-fundoplication dyspepsia.

Refractory Gastroesophageal Reflux Disease: A Management Update.

Gastroesophageal reflux disease (GERD) is one of the most frequent gastrointestinal disorders. Proton pump inhibitors (PPIs) are effective in healing lesions and improving symptoms in most cases, although up to 40% of GERD patients do not respond adequately to PPI therapy. Refractory GERD (rGERD) is one of the most challenging problems, given its impact on the quality of life and consumption of health care resources. The definition of rGERD is a controversial topic as it has not been unequivocally established. Indeed, some patients unresponsive to PPIs who experience symptoms potentially related to GERD may not have GERD; in this case the definition could be replaced with "reflux-like PPI-refractory symptoms." Patients with persistent reflux-like symptoms should undergo a diagnostic workup aimed at finding objective evidence of GERD through endoscopic and pH-impedance investigations. The management strategies regarding rGERD, apart from a careful check of patient's compliance with PPIs, a possible change in the timing of their administration and the choice of a PPI with a different metabolic pathway, include other pharmacologic treatments. These include histamine-2 receptor antagonists (H2RAs), alginates, antacids and mucosal protective agents, potassium competitive acid blockers (PCABs), prokinetics, gamma aminobutyric acid-B (GABA-B) receptor agonists and metabotropic glutamate receptor-5 (mGluR5) antagonists, and pain modulators. If there is no benefit from medical therapy, but there is objective evidence of GERD, invasive antireflux options should be evaluated after having carefully explained the risks and benefits to the patient. The most widely performed invasive antireflux option remains laparoscopic antireflux surgery (LARS), even if other, less invasive, interventions have been suggested in the last few decades, including endoscopic transoral incisionless fundoplication (TIF), magnetic sphincter augmentation (LINX) or radiofrequency therapy (Stretta). Due to the different mechanisms underlying rGERD, the most effective strategy can vary, and it should be tailored to each patient. The aim of this paper is to review the different management options available to successfully deal with rGERD.

Changes in the disease-specific quality of life following Dor fundoplication. A multicentre cross-sectional study.

BACKGROUND: Gastrooesophageal reflux disease (GERD) is a spectrum of symptoms arising from the laxity of the cardio-oesophageal junction. Anti-reflux surgery is reserved for patients with refractory GERD. Anterior partial fundoplication (Dor) is a regularly performed anti-reflux surgery in Malaysia. We intend to determine the improvement in disease-specific quality of life in our patients after surgery. METHODS: A multicentre cross-sectional study was conducted to assess patients' improvement in disease-specific quality of life after Dor fundoplication. Ethics approval was obtained from our institutional review board. Patients between the ages of 18 and 65 years who underwent Dor fundoplication within the past five years were assessed using the GERD HRQL as well as the VISICK score via telephone interview. We excluded cases of revision surgery. RESULTS: Out of 129 patients screened, 55 patients were included. We found a significant improvement in patients' GERD HRQL score with the pre-operative mean score of 28.3 ± 9.39 and 6.55 ± 8.52 post-operatively, p < 0.01.50.9% of patients reported a VISICK score of 1. However, we noticed a deterioration in the GERD HRQL and VISICK score in patients followed up four years after surgery. This consisted of 25.5% of total patients. CONCLUSION: Dor Fundoplication improves the overall disease-specific quality of life in patients with refractory GERD in the short term period. Recurrence of symptoms causing a deterioration in the quality of life is seen in patients followed up beyond four years of index surgery.

Antireflux Mucosectomy Band (ARM-b) in Treatment of Refractory Gastroesophageal Reflux Disease After Bariatric Surgery.

Laparoscopic sleeve gastrectomy has become the most commonly used bariatric surgery worldwide. However, there are a proportion of patients who present with a refractory GERD after this procedure. In these patients, when surgical conversion to RYGPB is not possible or declined, we propose to describe the results of an endoscopic antireflux mucosectomy band (ARM-b) technique in 6 LSG patients with refractory GERD. The technical feasibility was 100%; 5 out of 6 patients had a clinical response with a reduction of the GERD-HRQL score of > 50%. Two patients had adverse events: one esophageal stricture and one benign bleeding. ARM-b is feasible and potentially effective to treat patients with refractory GERD after LSG.

Evaluation of the Additive Effect of Domperidone on Patients with Refractory Gastroesophageal Reflux Disease; A Randomized Double Blind Clinical Trial.

BACKGROUND Gastroesophageal reflux disease (GERD) is a common problem with annoying symptoms. It is associated with negative impact on quality of life. Prokinetic agents may be used in combination with acid suppression agents as an adjunctive in patients with GERD refractory to proton pump inhibitors (PPI) therapy, rather than as sole treatment. This study aimed to evaluate the efficacy of combination of PPI with domperidone (a prokinetic agent) compared with PPI alone in the treatment of patients with refractory GERD. METHODS This study was a double blind clinical trial on 29 patients with GERD refractory to PPI during the period of one month. By randomization, the patients were divided into two groups. Group A was treated by pantoprazole 40 mg twice daily and domperidone three times a day for a month, while group B was treated by pantoprazole 40 mg twice daily and placebo three times a day. In this study endoscopy was performed to evaluate the prevalence of erosive esophagitis, non-erosive reflux, and hiatal hernia. Manometry was conducted to study the prevalence of dysmotility. GERD symptom questionnaires including the Gastrointestinal Symptom Rating Scale (GSRS), Carlson Dennett, and the Medical Outcomes Study Short Form-36 health survey (SF36) were used before and after treatment for screening GERD and assessing treatment response. RESULTS There were 17 (58.62%) women and 12 (41.37%) men. The prevalence of erosive esophagitis and non-erosive reflux, was 10.34% and 89.66%, respectively. There was a significant difference comparing reflux symptoms before and after treatment between the two groups according to reflux and Carlson Dennett questionnaires. At the end of the study, symptoms of reflux significantly improved by treatment. Although, the quality of life questionnaire scores improved by treatment, there was no statistically significant difference in response to treatment between the two groups. CONCLUSION In this research, we showed that adding domperidone to PPI could not make any improvement in patients with refractory reflux regarding the quality of life and improving the symptoms.

Retrospective Analysis of Eosinophilic Esophagitis in Patients with Refractory Gastroesophageal Reflux Disease.

Introduction Eosinophilic esophagitis (EoE) is not a common differential diagnosis in patients with longstanding refractory gastroesophageal reflux disease (GERD). The aim of this retrospective analysis was to assess the prevalence of EoE in patients with refractory GERD. Methods This retrospective analysis was performed in the Gastroenterology Department of a tertiary care institute in Karachi, Pakistan. Records of esophagogastroduodenoscopy (EGD) with esophageal biopsy from January 2016 till December 2018 were included. Results There were 16 (7.7%) patients of refractory GERD diagnosed with EoE. There were more females than males (5:3). The median age was 58 years (range: 41-63 years). Dysphagia was the chief complaint leading to EGD followed by food impaction and heartburn. The median duration of symptoms was 46.5 months (range: 22-65 months). Erosive esophagitis, white plaques, and friability are common endoscopic findings; however, strictures are also not uncommon. Conclusion Eosinophilic esophagitis is not uncommon in patients with refractory GERD. It may present with dysphagia, heartburn, and food impaction. Old patients with longstanding GERD, positive for atopy, not responding to gastric acid inhibitors must be considered for EoE screening via EGD and esophageal biopsy.

Critical appraisal of Rome IV criteria: hypersensitive esophagus does belong to gastroesophageal reflux disease spectrum.

The Rome IV Committee introduced a major change in the classification of functional gastrointestinal disorders, proposing a more restrictive definition of gastroesophageal reflux disease (GERD). It was suggested that hypersensitive esophagus (HE) may sit more firmly within the functional realm. It was suggested that GERD diagnosis should be based upon abnormal acid exposure time (AET) only, implying no advantage of impedance-pH over pH monitoring. Symptom association probability (SAP), symptom index (SI) and heartburn relief with proton pump inhibitor (PPI) therapy were regarded as unreliable, whereas a lack of response to PPI was considered as evidence of functional heartburn. These assumptions are contradicted by numerous studies showing the clinical relevance of weakly acidic refluxes and the diagnostic utility of SAP, SI and new impedance parameters, namely the post-reflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI). The PSPW index and MNBI provide significant diagnostic advantage, particularly in patients with normal AET who can be classified as HE when both parameters are abnormal, even though SAP and SI are negative. Visceral pain modulators are recommended by the Rome IV Committee despite scanty evidence of efficacy, but a positive outcome with medical or surgical anti-reflux treatment has been reported by several studies of HE patients. Therefore, we believe that patients with endoscopy-negative heartburn should be investigated by means of impedance-pH monitoring with analysis of PSPW index and MNBI: such an approach provides accurate identification of HE cases, who remain, in our opinion, within the realm of GERD and should be treated accordingly.

The added diagnostic value of postreflux swallow-induced peristaltic wave index and nocturnal baseline impedance in refractory reflux disease studied with on-therapy impedance-pH monitoring.

BACKGROUND: On-therapy impedance-pH monitoring in proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) yielded conflicting results. We aimed to assess the diagnostic value of postreflux swallow-induced peristaltic wave (PSPW) index and mean nocturnal baseline impedance (MNBI) in PPI-refractory heartburn. METHODS: On-therapy impedance-pH tracings from 189 consecutive patients with PPI-refractory heartburn were blindly reviewed. Patients were subdivided into refractory reflux esophagitis (RRE), healed reflux esophagitis (HRE), non-erosive reflux disease (NERD), and functional heartburn (FH) according to endoscopic and conventional impedance-pH findings. The diagnostic accuracy of PSPW index and MNBI in separating NERD from FH was assessed with receiver-operating-characteristic (ROC) analysis. Objectively documented persistent reflux remission at 3-year follow-up in 53 patients who underwent laparoscopic fundoplication served to evaluate PSPW index and MNBI as independent predictors of PPI-refractory GERD confirmed by positive surgical outcome. KEY RESULTS: Median PSPW index and MNBI values were significantly lower in 39 RRE (16%; 1145 Ω) than in 41 HRE (25%; 1741 Ω) and in 68 NERD (29%; 2374 Ω) patients, and in all three GERD subgroups compared to 41 FH cases (67%; 3488 Ω) (P<.008). At ROC analysis, comparing NERD to FH the area under the curve was 0.886 with PSPW index and 0.677 with MNBI (P=.005). PSPW index was an independent predictor of PPI-refractory GERD (odds ratio 0.6983, P=.012). CONCLUSIONS & INFERENCES: At on-therapy impedance-pH monitoring, PSPW index and MNBI efficiently distinguish PPI-refractory NERD from FH. The PSPW index represents an independent predictor of PPI-refractory GERD.